Determinants of Cytomegalovirus Infection Outcomes in Solid Organ Transplant Recipients

Abstract

Cytomegalovirus (CMV) is the most common opportunistic post-transplant infection. Although important advances have been made in the management and prevention of post-transplant CMV, current strategies for monitoring and prevention still show significant limitations. Such gaps create opportunities to understand the determinants of viremia and disease episodes that occur despite the use of antiviral prophylaxis and pre-emptive antiviral therapy. Straddling the boundaries between clinical and basic science, in this PhD thesis I explore the potential utility and limitations of both molecular and immunological biomarker monitoring of Cytomegalovirus in predicting viral replication/disease and assessing therapeutic response. Additionally, I investigate the biological relevance of selected viral and host biomarkers as determinants of viral infection outcomes. This thesis is comprised of a series of 5 studies in which I examine the use of: viral DNA monitoring to assess responses to antiviral therapy during CMV disease (Chapter 2); viral DNA monitoring to predict viral replication/disease post antiviral prophylaxis (Chapter 3); interferon-gamma monitoring in the virus-specific immune response during viral replication (Chapter 4); host chemokine monitoring in the virus-specific immune response during viral replication (Chapter 5); and virus microRNA monitoring to assess the response to antiviral therapy during Cytomegalovirus disease (Chapter 6). Together, these studies highlight novel aspects of the virus-host interaction that contribute to the regulation, or loss thereof, of CMV replication in solid organ transplant recipients.